CS207578B2 - Method of preparation of the proline derivatives - Google Patents
Method of preparation of the proline derivatives Download PDFInfo
- Publication number
- CS207578B2 CS207578B2 CS77925A CS92577A CS207578B2 CS 207578 B2 CS207578 B2 CS 207578B2 CS 77925 A CS77925 A CS 77925A CS 92577 A CS92577 A CS 92577A CS 207578 B2 CS207578 B2 CS 207578B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- proline
- acid
- formula
- group
- methyl
- Prior art date
Links
- 150000003147 proline derivatives Chemical class 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 164
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 229960002429 proline Drugs 0.000 claims description 289
- -1 furthermore Chemical group 0.000 claims description 220
- 239000000243 solution Substances 0.000 claims description 150
- 239000002253 acid Substances 0.000 claims description 101
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 230000008569 process Effects 0.000 claims description 32
- 229930182821 L-proline Natural products 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 5
- SRIPWKGWOAOUEH-GDVGLLTNSA-N (2s)-1-(2-sulfanylpropanoyl)pyrrolidine-2-carboxylic acid Chemical compound CC(S)C(=O)N1CCC[C@H]1C(O)=O SRIPWKGWOAOUEH-GDVGLLTNSA-N 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 150000001447 alkali salts Chemical class 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
- 239000005541 ACE inhibitor Substances 0.000 abstract 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 111
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 109
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 78
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- 239000000047 product Substances 0.000 description 40
- 229960000583 acetic acid Drugs 0.000 description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 37
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 35
- 229910002027 silica gel Inorganic materials 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 32
- 238000003756 stirring Methods 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- HYIXVZHJZDSDBA-LURJTMIESA-N (2s)-1-(3-sulfanylpropanoyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CCS HYIXVZHJZDSDBA-LURJTMIESA-N 0.000 description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 13
- 235000011114 ammonium hydroxide Nutrition 0.000 description 13
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 11
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 9
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 8
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- FAKRSMQSSFJEIM-MLWJPKLSSA-N (2s)-1-(2-methyl-3-sulfanylpropanoyl)pyrrolidine-2-carboxylic acid Chemical compound SCC(C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-MLWJPKLSSA-N 0.000 description 6
- IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 230000010933 acylation Effects 0.000 description 6
- 238000005917 acylation reaction Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 6
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- KJXKOUXJZOOEDG-ZETCQYMHSA-N (2s)-1-(4-sulfanylbutanoyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CCCS KJXKOUXJZOOEDG-ZETCQYMHSA-N 0.000 description 5
- 108010064733 Angiotensins Proteins 0.000 description 5
- 102000015427 Angiotensins Human genes 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229940099112 cornstarch Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000020477 pH reduction Effects 0.000 description 5
- 229960003424 phenylacetic acid Drugs 0.000 description 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 5
- 150000003573 thiols Chemical class 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- 102000005862 Angiotensin II Human genes 0.000 description 4
- 101800000733 Angiotensin-2 Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000005915 ammonolysis reaction Methods 0.000 description 4
- 229950006323 angiotensin ii Drugs 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 4
- UIJGNTRUPZPVNG-UHFFFAOYSA-N benzenecarbothioic s-acid Chemical compound SC(=O)C1=CC=CC=C1 UIJGNTRUPZPVNG-UHFFFAOYSA-N 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- WQDRQHQJTRGMCX-UHFFFAOYSA-N 3-(acetamidomethylsulfanyl)-2-methylpropanoic acid Chemical compound OC(=O)C(C)CSCNC(C)=O WQDRQHQJTRGMCX-UHFFFAOYSA-N 0.000 description 3
- MXTKDWZKIQZANR-UHFFFAOYSA-N 3-[(4-methoxyphenyl)methylsulfanyl]-2-methylpropanoic acid Chemical compound COC1=CC=C(CSCC(C)C(O)=O)C=C1 MXTKDWZKIQZANR-UHFFFAOYSA-N 0.000 description 3
- VFVHNRJEYQGRGE-UHFFFAOYSA-N 3-acetylsulfanyl-2-methylpropanoic acid Chemical compound OC(=O)C(C)CSC(C)=O VFVHNRJEYQGRGE-UHFFFAOYSA-N 0.000 description 3
- AFUWKGZPMVUKIN-UHFFFAOYSA-N 4-bromo-2-methylbutanoic acid Chemical compound OC(=O)C(C)CCBr AFUWKGZPMVUKIN-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- DJVJZONPMOOVCU-UHFFFAOYSA-N n-(hydroxymethyl)propanamide Chemical compound CCC(=O)NCO DJVJZONPMOOVCU-UHFFFAOYSA-N 0.000 description 1
- 229960002460 nitroprusside Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 229960001732 pipemidic acid Drugs 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920000172 poly(styrenesulfonic acid) Polymers 0.000 description 1
- 229940005642 polystyrene sulfonic acid Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- GAPYKZAARZMMGP-UHFFFAOYSA-N pyridin-1-ium;acetate Chemical compound CC(O)=O.C1=CC=NC=C1 GAPYKZAARZMMGP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- LUDPWTHDXSOXDX-UHFFFAOYSA-N s-(3-chloro-2-methyl-3-oxopropyl) ethanethioate Chemical compound ClC(=O)C(C)CSC(C)=O LUDPWTHDXSOXDX-UHFFFAOYSA-N 0.000 description 1
- RJGDTGFFRQCKFO-UHFFFAOYSA-N s-(4-hydroxybutan-2-yl) ethanethioate Chemical compound OCCC(C)SC(C)=O RJGDTGFFRQCKFO-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- 239000003774 sulfhydryl reagent Substances 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- MESKMUAFJDWOAR-QMMMGPOBSA-N tert-butyl (2s)-piperidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCCN1 MESKMUAFJDWOAR-QMMMGPOBSA-N 0.000 description 1
- FVBHYZVVSXFCOO-UHFFFAOYSA-N tert-butyl hydrogen sulfate Chemical compound CC(C)(C)OS(O)(=O)=O FVBHYZVVSXFCOO-UHFFFAOYSA-N 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- DTMHTVJOHYTUHE-UHFFFAOYSA-N thiocyanogen Chemical compound N#CSSC#N DTMHTVJOHYTUHE-UHFFFAOYSA-N 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 150000008111 thiosulfinates Chemical class 0.000 description 1
- GWIKYPMLNBTJHR-UHFFFAOYSA-M thiosulfonate group Chemical group S(=S)(=O)[O-] GWIKYPMLNBTJHR-UHFFFAOYSA-M 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
- C07C53/19—Acids containing three or more carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS792330A CS207580B2 (cs) | 1976-02-13 | 1979-04-05 | Způsob přípravy průlinových derivátů |
| CS792329A CS207579B2 (cs) | 1976-02-13 | 1979-04-05 | Způsob přípravy prolinových derivátů |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/657,792 US4046889A (en) | 1976-02-13 | 1976-02-13 | Azetidine-2-carboxylic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS207578B2 true CS207578B2 (en) | 1981-08-31 |
Family
ID=24638681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS77925A CS207578B2 (en) | 1976-02-13 | 1977-02-11 | Method of preparation of the proline derivatives |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US4046889A (fr) |
| JP (3) | JPS58189113A (fr) |
| BE (1) | BE851361A (fr) |
| CS (1) | CS207578B2 (fr) |
| DD (2) | DD283998A5 (fr) |
| HU (1) | HU185576B (fr) |
| SU (2) | SU850001A3 (fr) |
| ZA (1) | ZA77313B (fr) |
Families Citing this family (199)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4206122A (en) * | 1978-04-14 | 1980-06-03 | E. R. Squibb & Sons, Inc. | Derivatives of pyrrolidinecarboxaldehyde and piperidinecarboxaldehyde and intermediates therefor |
| US4105776A (en) * | 1976-06-21 | 1978-08-08 | E. R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
| US4339600A (en) * | 1976-05-10 | 1982-07-13 | E. R. Squibb & Sons, Inc. | Compounds for alleviating angiotensin related hypertension |
| US4199512A (en) * | 1976-05-10 | 1980-04-22 | E. R. Squibb & Sons, Inc. | Compounds for alleviating hypertension |
| US4176235A (en) * | 1976-12-03 | 1979-11-27 | E. R. Squibb & Sons, Inc. | Substituted acyl derivatives of amino acids |
| US4192878A (en) * | 1976-12-03 | 1980-03-11 | E. R. Squibb & Sons, Inc. | Derivatives of thiazolidinecarboxylic acids and related acids |
| US4198517A (en) * | 1976-12-03 | 1980-04-15 | E. R. Squibb & Sons, Inc. | Histidine derivatives |
| US4206121A (en) * | 1976-12-03 | 1980-06-03 | E. R. Squibb & Sons, Inc. | Substituted acyl derivatives of amino acids |
| US4175199A (en) * | 1976-12-03 | 1979-11-20 | E. R. Squibb & Sons, Inc. | Substituted acyl derivatives of amino acids |
| US4237129A (en) * | 1976-12-03 | 1980-12-02 | E. R. Squibb & Sons, Inc. | Derivatives of thiazolidinecarboxylic acids and related acids |
| US4178291A (en) * | 1976-12-03 | 1979-12-11 | E. R. Squibb & Sons, Inc. | Substituted acyl derivatives of amino acids |
| US4237134A (en) * | 1976-12-03 | 1980-12-02 | E. R. Squibb & Sons, Inc. | Derivatives of thiazolidinecarboxylic acids and related acids |
| US4116962A (en) * | 1976-12-03 | 1978-09-26 | E. R. Squibb & Sons, Inc. | Pyrrolidine and piperidine-2-carboxylic acid derivatives |
| US4091024A (en) * | 1976-12-03 | 1978-05-23 | E. R. Squibb & Sons, Inc. | Pyrrolidine and piperidine-2-carboxylic acid derivatives |
| US4228077A (en) * | 1976-12-03 | 1980-10-14 | E. R. Squibb & Sons, Inc. | N-[2-(mercaptoalkyl)-3-mercaptoalkanoyl]-l-tryptophanes |
| US4129566A (en) * | 1978-02-15 | 1978-12-12 | E. R. Squibb & Sons, Inc. | Derivatives of dehydrocyclicimino acids |
| US4284780A (en) * | 1977-01-17 | 1981-08-18 | E. R. Squibb & Sons, Inc. | Amino acid derivatives |
| US4284779A (en) * | 1977-01-17 | 1981-08-18 | E. R. Squibb & Sons, Inc. | Amino acid derivatives |
| US4113715A (en) * | 1977-01-17 | 1978-09-12 | E. R. Squibb & Sons, Inc. | Amino acid derivatives |
| US4154937A (en) * | 1977-02-11 | 1979-05-15 | E. R. Squibb & Sons, Inc. | Hydroxycarbamoylalkylacylpipecolic acid compounds |
| US4151172A (en) * | 1977-08-11 | 1979-04-24 | E. R. Squibb & Sons, Inc. | Phosphonoacyl prolines and related compounds |
| IT7851510A0 (it) * | 1977-10-28 | 1978-10-16 | Sandoz Ag | Ammidi di amminoacidi ciclici loro preparazione e loro applicazione quali medicamenti |
| US4217347A (en) * | 1977-12-27 | 1980-08-12 | E. R. Squibb & Sons, Inc. | Method of treating hypertension and medicaments therefor |
| US4241076A (en) * | 1978-02-21 | 1980-12-23 | E. R. Squibb & Sons, Inc. | Halogenated substituted mercaptoacylamino acids |
| US4154935A (en) * | 1978-02-21 | 1979-05-15 | E. R. Squibb & Sons, Inc. | Halogen substituted mercaptoacylamino acids |
| US4206137A (en) * | 1978-03-27 | 1980-06-03 | E. R. Squibb & Sons, Inc. | Thioalkanoylalkanoic acid compounds |
| US4282235A (en) * | 1978-05-22 | 1981-08-04 | E. R. Squibb & Sons, Inc. | Derivatives of thiazolidinecarboxylic acids and related acids |
| JPS559058A (en) * | 1978-07-06 | 1980-01-22 | Dainippon Pharmaceut Co Ltd | 1-(3-mercapto-2-methylpropanoyl)prolyl amino acid derivative |
| US4179568A (en) * | 1978-07-31 | 1979-12-18 | E. R. Squibb & Sons, Inc. | (N-lower alkyl-3,5-dioxo-3-pyrrolidinyl)thioalkanoylpyrrolidine-and piperidine-carboxylic acid compounds |
| US4154934A (en) * | 1978-08-11 | 1979-05-15 | E. R. Squibb & Sons, Inc. | Mercaptoacylamino derivatives of heterocyclic carboxylic acids |
| US4316906A (en) * | 1978-08-11 | 1982-02-23 | E. R. Squibb & Sons, Inc. | Mercaptoacyl derivatives of substituted prolines |
| JPS5531022A (en) * | 1978-08-24 | 1980-03-05 | Yoshitomi Pharmaceut Ind Ltd | Hydroxamic acid derivative and its preparation |
| US4226775A (en) * | 1979-06-01 | 1980-10-07 | American Cyanamid Company | Substituted thio-substituted benzyl-propionyl-L-prolines |
| US4698355A (en) * | 1979-08-14 | 1987-10-06 | University Of Miami | Anti-hypertensive agents |
| US4690939A (en) * | 1979-08-14 | 1987-09-01 | University Of Miami | Anti-hypertensive agents |
| US4698356A (en) * | 1979-08-14 | 1987-10-06 | University Of Miami | Anti-hypertensive agents |
| US4695577A (en) * | 1979-08-14 | 1987-09-22 | University Of Miami | Anti-hypertensive agents |
| US4690937A (en) * | 1979-08-14 | 1987-09-01 | University Of Miami | Anti-hypertensive agents |
| ZA794723B (en) * | 1978-09-11 | 1980-08-27 | Univ Miami | Anti-hypertensive agents |
| US4690940A (en) * | 1979-08-14 | 1987-09-01 | University Of Miami | Anti-hypertensive agents |
| US4690938A (en) * | 1979-08-14 | 1987-09-01 | University Of Miami | Anti-hypertensive agents |
| JPS5829950B2 (ja) * | 1978-10-05 | 1983-06-25 | ウェルファイド株式会社 | 環状イミノカルボン酸誘導体およびその塩類 |
| US4168267A (en) * | 1978-10-23 | 1979-09-18 | E. R. Squibb & Sons, Inc. | Phosphinylalkanoyl prolines |
| US4198509A (en) * | 1978-10-30 | 1980-04-15 | E. R. Squibb & Sons, Inc. | Mercaptoacylpiperazine carboxylic acid compounds |
| US4483861A (en) * | 1978-10-31 | 1984-11-20 | Santen Pharmaceutical Co., Ltd. | Antihypertensive sulfur-containing compounds |
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| AU2019384564B2 (en) | 2018-11-21 | 2023-11-23 | Icu Medical, Inc. | Antimicrobial device comprising a cap with ring and insert |
| RS66416B1 (sr) | 2019-01-18 | 2025-02-28 | Astrazeneca Ab | 6'-[[(1s,3s)-3-[[5-(difluorometoksi)-2-pirimidinil]amino]ciklopentil]amino][1(2h),3'-bipiridin]-2-on kao inhibitor pcsk9 i metode njegove primene |
| CA3204371A1 (fr) | 2020-12-07 | 2022-06-16 | Icu Medical, Inc. | Capuchons, systemes et procedes de dialyse peritoneale |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091024A (en) * | 1976-12-03 | 1978-05-23 | E. R. Squibb & Sons, Inc. | Pyrrolidine and piperidine-2-carboxylic acid derivatives |
-
1976
- 1976-02-13 US US05/657,792 patent/US4046889A/en not_active Expired - Lifetime
-
1977
- 1977-01-19 ZA ZA770313A patent/ZA77313B/xx unknown
- 1977-02-11 DD DD77331255A patent/DD283998A5/de active Search and Examination
- 1977-02-11 CS CS77925A patent/CS207578B2/cs unknown
- 1977-02-11 BE BE174885A patent/BE851361A/fr not_active IP Right Cessation
- 1977-02-11 DD DD77331256A patent/DD283999A5/de unknown
-
1978
- 1978-03-09 US US05/884,791 patent/US4154840A/en not_active Expired - Lifetime
- 1978-03-31 SU SU782595500A patent/SU850001A3/ru active
- 1978-03-31 SU SU782595499A patent/SU845775A3/ru active
-
1982
- 1982-10-01 HU HU823154A patent/HU185576B/hu unknown
-
1983
- 1983-03-15 JP JP58045277A patent/JPS58189113A/ja active Pending
- 1983-03-15 JP JP58045275A patent/JPS6059226B2/ja not_active Expired
- 1983-03-15 JP JP58045276A patent/JPS6056705B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DD283998A5 (de) | 1990-10-31 |
| SU850001A3 (ru) | 1981-07-23 |
| JPS58189158A (ja) | 1983-11-04 |
| BE851361A (fr) | 1977-08-11 |
| DD283999A5 (de) | 1990-10-31 |
| US4154840A (en) | 1979-05-15 |
| US4046889A (en) | 1977-09-06 |
| SU845775A3 (ru) | 1981-07-07 |
| JPS6056705B2 (ja) | 1985-12-11 |
| JPS58189159A (ja) | 1983-11-04 |
| JPS6059226B2 (ja) | 1985-12-24 |
| JPS58189113A (ja) | 1983-11-04 |
| HU185576B (en) | 1985-02-28 |
| ZA77313B (en) | 1977-11-30 |
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